Since I joined Dr. S. M. Jazwinski's laboratory in 2004 as postdoctoral associate, I've been participating in two research projects to study genetics of human longevity, as part of multidisciplinary programs. These are population-based association studies, and the goal is to determine the genetic basis of healthy aging employing long-lived (>89 years old) human subjects. While recruiting the human subjects residing in Louisiana, we encountered rare families in which siblings tend to live exceptionally long. This finding further supports the idea that the ability to survive to old age is under genetic influence and led us to hypothesize that the long-lived siblings share common genetic variants. Taking advantage of these longevous families and the resources from the ongoing research projects, I propose to study the long-lived siblings with model-free linkage methods to identify the genetic variants of common ancestry. The specific aims are: (1) Define potential genomic regions by genome-wide scanning. Using blood samples, we will genotype the longevous subjects at 811 short-tandem repeat (STR) loci and Identify potential regions that are excessively shared among the long-lived siblings;(2) Narrow down the potential regions to smaller candidate regions by using more STR markers. As marker density increases, one can extract more inheritance information of the region of interest, which add more accuracy and power to the analysis;(3) Dissect the candidate regions with haplotype-based association analysis. We will find haplotype-tagging SNPs (htSNPs) and determine any significant association of the htSNPs with longevity. Achieving these aims will lead to identification of the genetic variants associated with exceptional longevity. My long-term career goal is, as an independent research scientist, to perform systematic, in-depth studies of genes carrying the genetic variants and understand their role in the progression of aging and age-related changes. During the award period, I would be devoting 100% of my time and effort to completing the proposed research and career development plans, acquiring all the necessary knowledge, skills, and training for my career development. The training activities include attending several courses with various topics in human genetics and statistical genetics during the first three years. Toward the end of the award period, I plan to secure a major research grant and an independent position. Relevance to public health: Close relatives of long-lived people tend to live longer than those of short-lived people because the trait of longevity runs in these exceptional families. My research plan is focused on isolating the genetic factors that are shared by the exceptionally longevous family members.